UA90048C2 - Кондиціонована композиція крові і спосіб її одержання - Google Patents

Кондиціонована композиція крові і спосіб її одержання

Info

Publication number
UA90048C2
UA90048C2 UAA200810851A UAA200810851A UA90048C2 UA 90048 C2 UA90048 C2 UA 90048C2 UA A200810851 A UAA200810851 A UA A200810851A UA A200810851 A UAA200810851 A UA A200810851A UA 90048 C2 UA90048 C2 UA 90048C2
Authority
UA
Ukraine
Prior art keywords
conditioned blood
production
blood composition
conditioned
blood compositions
Prior art date
Application number
UAA200810851A
Other languages
English (en)
Russian (ru)
Inventor
Юлио Рейнекке
Петер Велинг
Original Assignee
Ортоген Аг
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=37965046&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=UA90048(C2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Ортоген Аг filed Critical Ортоген Аг
Publication of UA90048C2 publication Critical patent/UA90048C2/uk

Links

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14Blood; Artificial blood
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18Growth factors; Growth regulators
    • A61K38/1825Fibroblast growth factor [FGF]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18Growth factors; Growth regulators
    • A61K38/1833Hepatocyte growth factor; Scatter factor; Tumor cytotoxic factor II
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18Growth factors; Growth regulators
    • A61K38/1841Transforming growth factor [TGF]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18Growth factors; Growth regulators
    • A61K38/1858Platelet-derived growth factor [PDGF]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/191Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • A61K38/2006IL-1
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • A61K38/2026IL-4
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • A61K38/204IL-6
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • A61K38/2066IL-10
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • A61K38/2086IL-13 to IL-16
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22Hormones
    • A61K38/30Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/02Blood transfusion apparatus
    • A61M1/0209Multiple bag systems for separating or storing blood components
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • AHUMAN NECESSITIES
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    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/04Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
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    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
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    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/08Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Genetics & Genomics (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Endocrinology (AREA)
  • Wood Science & Technology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • General Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Neurology (AREA)
  • Anesthesiology (AREA)
  • Plant Pathology (AREA)
  • Cell Biology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Virology (AREA)
  • Biochemistry (AREA)
  • Orthopedic Medicine & Surgery (AREA)

Abstract

Винахід стосується способу одержання кондиціонованих композицій крові, які містять індуковані фактори, а також їх застосування для лікування або профілактики захворювання тіла людини або тварини.
UAA200810851A 2006-02-03 2007-02-02 Кондиціонована композиція крові і спосіб її одержання UA90048C2 (uk)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE102006005016A DE102006005016A1 (de) 2006-02-03 2006-02-03 Konditionierte Blutzusammensetzung und Verfahren zu deren Herstellung

Publications (1)

Publication Number Publication Date
UA90048C2 true UA90048C2 (uk) 2010-03-25

Family

ID=37965046

Family Applications (1)

Application Number Title Priority Date Filing Date
UAA200810851A UA90048C2 (uk) 2006-02-03 2007-02-02 Кондиціонована композиція крові і спосіб її одержання

Country Status (24)

Country Link
US (1) US20090047242A1 (uk)
EP (2) EP1984006B1 (uk)
JP (1) JP2009525297A (uk)
KR (1) KR20080100425A (uk)
CN (1) CN101378768A (uk)
AT (1) ATE446100T1 (uk)
AU (1) AU2007213996A1 (uk)
BR (1) BRPI0707360A2 (uk)
CA (1) CA2640002A1 (uk)
CY (1) CY1109735T1 (uk)
DE (2) DE102006005016A1 (uk)
DK (1) DK1984006T3 (uk)
EA (1) EA014435B1 (uk)
ES (1) ES2335446T3 (uk)
HK (1) HK1125835A1 (uk)
HR (1) HRP20090684T1 (uk)
MX (1) MX2008009807A (uk)
PL (1) PL1984006T3 (uk)
PT (1) PT1984006E (uk)
RS (1) RS51247B (uk)
SI (1) SI1984006T1 (uk)
UA (1) UA90048C2 (uk)
WO (1) WO2007090569A1 (uk)
ZA (1) ZA200805975B (uk)

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EP2259774B1 (en) * 2008-02-27 2012-12-12 Biomet Biologics, LLC Methods and compositions for delivering interleukin-1 receptor antagonist
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DE102008028684A1 (de) * 2008-06-17 2009-12-24 Kopetzky, Robert, Dr. Blutbeutel
US8460227B2 (en) * 2008-11-17 2013-06-11 Arthrex, Inc. Cytokine concentration system
AU2010237191A1 (en) 2009-04-07 2011-11-03 Velin-Pharma A/S Method and device for treatment of conditions associated with inflammation or undesirable activation of the immune system
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US20110052561A1 (en) * 2009-08-27 2011-03-03 Biomet Biologics,LLC Osteolysis treatment
CA2773619C (en) 2009-09-10 2019-11-12 Svend Lindenberg Method for the preparation of micro-rna and its therapeutic application
DE202009017772U1 (de) 2009-12-10 2011-04-21 Orthogen Ag Kombinationspräparate mit Cytokin-Antagonist und Corticosteroid
EP2611456A2 (en) 2010-09-03 2013-07-10 Biomet Biologics, LLC Methods and compositions for delivering interleukin-1 receptor antagonist
DE102010042356A1 (de) * 2010-10-12 2012-04-12 Henke-Sass, Wolf Gmbh Behälter für die Herstellung einer konditionierten Blutzusammensetzung
US9011846B2 (en) 2011-05-02 2015-04-21 Biomet Biologics, Llc Thrombin isolated from blood and blood fractions
US9205110B2 (en) 2012-07-18 2015-12-08 Arthrex, Inc. Enhanced autologous growth factor production and delivery system
DE102012019088A1 (de) * 2012-09-28 2014-04-03 Orthogen Ag Antibakterielle Arzneimittelpräparate
SG11201506259WA (en) 2013-02-12 2015-09-29 Lacerta Technologies Inc Serum fraction of platelet-rich fibrin
US9950035B2 (en) 2013-03-15 2018-04-24 Biomet Biologics, Llc Methods and non-immunogenic compositions for treating inflammatory disorders
US9895418B2 (en) 2013-03-15 2018-02-20 Biomet Biologics, Llc Treatment of peripheral vascular disease using protein solutions
US10208095B2 (en) 2013-03-15 2019-02-19 Biomet Manufacturing, Llc Methods for making cytokine compositions from tissues using non-centrifugal methods
US9878011B2 (en) 2013-03-15 2018-01-30 Biomet Biologics, Llc Treatment of inflammatory respiratory disease using biological solutions
US9758806B2 (en) 2013-03-15 2017-09-12 Biomet Biologics, Llc Acellular compositions for treating inflammatory disorders
US10143725B2 (en) 2013-03-15 2018-12-04 Biomet Biologics, Llc Treatment of pain using protein solutions
US20140271589A1 (en) 2013-03-15 2014-09-18 Biomet Biologics, Llc Treatment of collagen defects using protein solutions
EP2829278A1 (de) * 2013-07-23 2015-01-28 Scientific BioTech GmbH Serum zur Behnandlung von Krankheiten
EP3074507B1 (en) 2013-11-26 2022-01-05 Biomet Biologics, LLC Methods of mediating macrophage phenotypes
WO2015085348A1 (en) * 2013-12-09 2015-06-18 Cytokine Medical Australia Pty Ltd Apparatus for producing therapeutically active proteins in blood and uses thereof
US10441635B2 (en) 2014-11-10 2019-10-15 Biomet Biologics, Llc Methods of treating pain using protein solutions
US9763800B2 (en) 2015-03-18 2017-09-19 Biomet C. V. Implant configured for hammertoe and small bone fixation
AU2017313163B2 (en) * 2016-08-17 2019-01-03 Orthogen Ag Anti-ageing pharmaceutical preparation
EP3613424A1 (en) 2018-08-23 2020-02-26 Orthogen AG Novel methods for the production of pharmaceutical agents
DE102021124752A1 (de) 2021-09-24 2023-03-30 Ad Lentus GmbH Autologes Therapeutikum und Verfahren zur Herstellung desselben
CN114146096B (zh) * 2021-11-25 2024-04-02 成都清科生物科技有限公司 一种富含细胞因子的条件血清的制备方法及应用

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Also Published As

Publication number Publication date
ES2335446T3 (es) 2010-03-26
AU2007213996A1 (en) 2007-08-16
SI1984006T1 (sl) 2010-02-26
EP2156841A1 (de) 2010-02-24
MX2008009807A (es) 2008-09-26
ATE446100T1 (de) 2009-11-15
DK1984006T3 (da) 2010-03-01
US20090047242A1 (en) 2009-02-19
KR20080100425A (ko) 2008-11-18
JP2009525297A (ja) 2009-07-09
WO2007090569A1 (de) 2007-08-16
WO2007090569A8 (de) 2008-02-28
ZA200805975B (en) 2010-08-25
DE502007001793D1 (de) 2009-12-03
PT1984006E (pt) 2010-01-20
HRP20090684T1 (hr) 2010-02-28
EP1984006A1 (de) 2008-10-29
EP1984006B1 (de) 2009-10-21
EA014435B1 (ru) 2010-12-30
CA2640002A1 (en) 2007-08-16
PL1984006T3 (pl) 2010-03-31
RS51247B (sr) 2010-12-31
CN101378768A (zh) 2009-03-04
CY1109735T1 (el) 2014-09-10
HK1125835A1 (en) 2009-08-21
EA200870222A1 (ru) 2008-12-30
DE102006005016A1 (de) 2007-08-16
BRPI0707360A2 (pt) 2011-05-03

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